A Safety and Efficacy Study of Refresh Optive® Gel Drops in Patients With Dry Eye Disease

• Sponsor: Allergan (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02280473
• Collaborator: (none)
• Enrollment: 188
• Locations: 10
• Arms: 2
• Actual Duration (Months): 4
• Patients Per Site: 18.8
• Patients Per Site Per Month: 4.7

Study Details

Study Description

Brief Summary

This study will evaluate the safety and efficacy o fRefresh Optive® Gel Drops in patients with dry eye disease.

Condition or Disease	Intervention/Treatment	Phase
Dry Eye Syndromes	Drug: Refresh Optive® Gel Drops; Drug: REFRESH LIQUIGEL®	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 188 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Actual Study Start Date: Nov 13, 2014
• Actual Primary Completion Date: Mar 16, 2015
• Actual Study Completion Date: Mar 16, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Refresh Optive® Gel Drops Refresh Optive® Gel Drops; 1-2 drops in each eye as needed at least 2 times daily for 30 days.	Drug: Refresh Optive® Gel Drops; Refresh Optive® Gel Drops; 1-2 drops in each eye as needed at least 2 times daily for 30 days.
Active Comparator: REFRESH LIQUIGEL® REFRESH LIQUIGEL®; 1-2 drops in each eye as needed at least 2 times daily for 30 days.	Drug: REFRESH LIQUIGEL®; REFRESH LIQUIGEL®; 1-2 drops in each eye as needed at least 2 times daily for 30 days.

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in the Ocular Surface Disease Index© (OSDI©) Score [Baseline, Day 30]

   The OSDI is a 12-question survey for patients to document their dry eye disease symptoms. The OSDI consists of a 5-point scale (0=none of the time and 4=all of the time), with higher scores representing greater disability. The scores are totaled over the 12 questions and converted to a score of 0-100 (0=no disability and 100=complete disability). A negative number change from baseline represents an improvement.

Secondary Outcome Measures

1. Change From Baseline in the OSDI© Score [Baseline, Day 7]

   The OSDI is a 12-question survey for patients to document their dry eye disease symptoms. The OSDI consists of a 5-point scale (0=none of the time and 4=all of the time), with higher scores representing greater disability. The scores are totaled over the 12 questions and converted to a score of 0-100 (0=no disability and 100=complete disability). A negative number change from baseline represents an improvement.

2. Change From Baseline in Tear Break-up Time (TBUT) [Baseline, Day 30]

   TBUT is the time required for dry spots to appear on the surface of the eye after blinking. The longer it takes, the more stable the tear film. A short TBUT is a sign of poor tear film. A positive number change from baseline indicates an increase in TBUT (improvement). The eye with shorter average TBUT at baseline is reported for each patient.

3. Change From Baseline in the Combined Corneal and Conjunctival Staining Scores [Baseline, Day 30]

   The cornea is the transparent front part of the eye which covers the iris and pupil. The conjunctiva is the clear membrane covering the white surface of the eye. The cornea is divided into 5 zones and the nasal and temporal conjunctiva is divided into 6 zones. The combined staining score is based on the sum of the five zones on the cornea and the six zones on the conjunctiva. Each zone is graded on a 0-5 scale (0=None; 1=trace; 2=mild; 3=moderate; 4=severe; 5=very severe), for a total score ranging from 0-55. The higher the score, the worse the dry eye condition. A negative number change from baseline represents a decrease in the severity of staining (improvement). The eye with higher score at baseline is reported for each subject.

4. Change From Baseline in the Schirmer Test [Baseline, Day 30]

   The Schirmer's Test measures the rate of the secretion of tears produced by the eye over 5 minutes. The results indicate the presence of dry eye. The eye with the lower value at Baseline was used for Analysis. Normal = greater than or equal to 15 millimeters (mm) of tears, Dry Eye = less than 15 mm of tears.. The smaller the number, the more severe the dry eye. A positive number change from Baseline indicates improvement. The eye with the lower value at baseline is used for each subject.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Current use of an artificial tear product

• Visual acuity of at least 20/32 (while wearing glasses, if necessary).

Exclusion Criteria:

• Use of contact lenses in the last 3 months, or anticipated use of contact lenses during the study

• Cataract surgery, laser-assisted in situ keratomileusis [LASIK], or photorefractive keratectomy, within the last 6 months

• Current eye infection or inflammation

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	North Bay Eye Associates	Petaluma	California	United States	94954
2	Eric M. White, OD, Inc.	San Diego	California	United States	92123
3	Eye Center Northeast	Bangor	Maine	United States	04401
4	Moyes Eye Center, PC	Kansas City	Missouri	United States	64154
5	Ophthalmology Associates	Saint Louis	Missouri	United States	63131
6	Comprehensive Eye Care, Ltd.	Washington	Missouri	United States	63090
7	Rochester Ophthalmological Group, PC	Rochester	New York	United States	14618
8	David W. Ferris & Associates, Inc.	Warwick	Rhode Island	United States	02888
9	Primary Eyecare Group, PC	Brentwood	Tennessee	United States	37027
10	The Eye Center at Southern College of Optometry	Memphis	Tennessee	United States	38104

Sponsors and Collaborators

• Allergan

Investigators

• Study Director: Medical Director, Allergan

Study Documents (Full-Text)

None provided.

More Information

Publications

• Lievens C, Berdy G, Douglass D, Montaquila S, Lin H, Simmons P, Carlisle-Wilcox C, Vehige J, Haque S. Evaluation of an enhanced viscosity artificial tear for moderate to severe dry eye disease: A multicenter, double-masked, randomized 30-day study. Cont Lens Anterior Eye. 2019 Aug;42(4):443-449. doi: 10.1016/j.clae.2018.12.003. Epub 2018 Dec 17.

• Responsible Party: Allergan
• ClinicalTrials.gov Identifier: NCT02280473
• Other Study ID Numbers: 11193X-001
• First Posted: Oct 31, 2014
• Last Update Posted: Apr 16, 2019
• Last Verified: Apr 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Dry Eye Syndromes; Keratoconjunctivitis Sicca; Carboxymethylcellulose Sodium

Study Results

Participant Flow

Arm/Group Title	Refresh Optive® Gel Drops	REFRESH LIQUIGEL®
Arm/Group Description	Refresh Optive® Gel Drops; 1-2 drops in each eye as needed at least 2 times daily for 30 days.	REFRESH LIQUIGEL®; 1-2 drops in each eye as needed at least 2 times daily for 30 days.
Period Title: Overall Study
STARTED	94	94
COMPLETED	93	91
NOT COMPLETED	1	3

Baseline Characteristics

Arm/Group Title	Refresh Optive® Gel Drops	REFRESH LIQUIGEL®	Total
Arm/Group Description	Refresh Optive® Gel Drops; 1-2 drops in each eye as needed at least 2 times daily for 30 days.	REFRESH LIQUIGEL®; 1-2 drops in each eye as needed at least 2 times daily for 30 days.	Total of all reporting groups
Overall Participants	94	94	188
Age, Customized (Number) [Number]
18 to less than 30 years	11 11.7%	13 13.8%	24 12.8%
30 to 40 years	11 11.7%	14 14.9%	25 13.3%
More than 40 years	72 76.6%	67 71.3%	139 73.9%
Sex: Female, Male (Count of Participants)
Female	78 83%	75 79.8%	153 81.4%
Male	16 17%	19 20.2%	35 18.6%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in the Ocular Surface Disease Index© (OSDI©) Score
Description	The OSDI is a 12-question survey for patients to document their dry eye disease symptoms. The OSDI consists of a 5-point scale (0=none of the time and 4=all of the time), with higher scores representing greater disability. The scores are totaled over the 12 questions and converted to a score of 0-100 (0=no disability and 100=complete disability). A negative number change from baseline represents an improvement.
Time Frame	Baseline, Day 30

Outcome Measure Data

Analysis Population Description

Intent-to-Treat: All randomized patients

Arm/Group Title	Refresh Optive® Gel Drops	REFRESH LIQUIGEL®
Arm/Group Description	Refresh Optive® Gel Drops; 1-2 drops in each eye as needed at least 2 times daily for 30 days.	REFRESH LIQUIGEL®; 1-2 drops in each eye as needed at least 2 times daily for 30 days.
Measure Participants	94	94
Baseline	42.44 (11.708)	40.43 (11.232)
Change from Baseline at Day 30	-10.29 (15.864)	-7.48 (16.592)

2. Secondary Outcome

Title	Change From Baseline in the OSDI© Score
Description	The OSDI is a 12-question survey for patients to document their dry eye disease symptoms. The OSDI consists of a 5-point scale (0=none of the time and 4=all of the time), with higher scores representing greater disability. The scores are totaled over the 12 questions and converted to a score of 0-100 (0=no disability and 100=complete disability). A negative number change from baseline represents an improvement.
Time Frame	Baseline, Day 7

Outcome Measure Data

Analysis Population Description

Intent-to-Treat: All randomized patients

Arm/Group Title	Refresh Optive® Gel Drops	REFRESH LIQUIGEL®
Arm/Group Description	Refresh Optive® Gel Drops; 1-2 drops in each eye as needed at least 2 times daily for 30 days.	REFRESH LIQUIGEL®; 1-2 drops in each eye as needed at least 2 times daily for 30 days.
Measure Participants	94	94
Baseline	42.44 (11.708)	40.43 (11.232)
Change from Baseline at Day 7	-5.74 (14.338)	-2.34 (12.294)

3. Secondary Outcome

Title	Change From Baseline in Tear Break-up Time (TBUT)
Description	TBUT is the time required for dry spots to appear on the surface of the eye after blinking. The longer it takes, the more stable the tear film. A short TBUT is a sign of poor tear film. A positive number change from baseline indicates an increase in TBUT (improvement). The eye with shorter average TBUT at baseline is reported for each patient.
Time Frame	Baseline, Day 30

Outcome Measure Data

Analysis Population Description

Intent-to-Treat: All randomized patients

Arm/Group Title	Refresh Optive® Gel Drops	REFRESH LIQUIGEL®
Arm/Group Description	Refresh Optive® Gel Drops; 1-2 drops in each eye as needed at least 2 times daily for 30 days.	REFRESH LIQUIGEL®; 1-2 drops in each eye as needed at least 2 times daily for 30 days.
Measure Participants	94	94
Baseline	5.38 (1.674)	5.40 (2.138)
Change from Baseline at Day 30 (N-94, 93)	0.84 (1.968)	0.70 (4.139)

4. Secondary Outcome

Title	Change From Baseline in the Combined Corneal and Conjunctival Staining Scores
Description	The cornea is the transparent front part of the eye which covers the iris and pupil. The conjunctiva is the clear membrane covering the white surface of the eye. The cornea is divided into 5 zones and the nasal and temporal conjunctiva is divided into 6 zones. The combined staining score is based on the sum of the five zones on the cornea and the six zones on the conjunctiva. Each zone is graded on a 0-5 scale (0=None; 1=trace; 2=mild; 3=moderate; 4=severe; 5=very severe), for a total score ranging from 0-55. The higher the score, the worse the dry eye condition. A negative number change from baseline represents a decrease in the severity of staining (improvement). The eye with higher score at baseline is reported for each subject.
Time Frame	Baseline, Day 30

Outcome Measure Data

Analysis Population Description

Intent-to-Treat: All randomized patients

Arm/Group Title	Refresh Optive® Gel Drops	REFRESH LIQUIGEL®
Arm/Group Description	Refresh Optive® Gel Drops; 1-2 drops in each eye as needed at least 2 times daily for 30 days.	REFRESH LIQUIGEL®; 1-2 drops in each eye as needed at least 2 times daily for 30 days.
Measure Participants	94	94
Baseline	10.9 (7.24)	11.8 (7.16)
Change from Baseline at Day 30 (N=93, 91)	-1.7 (4.66)	-2.0 (6.12)

5. Secondary Outcome

Title	Change From Baseline in the Schirmer Test
Description	The Schirmer's Test measures the rate of the secretion of tears produced by the eye over 5 minutes. The results indicate the presence of dry eye. The eye with the lower value at Baseline was used for Analysis. Normal = greater than or equal to 15 millimeters (mm) of tears, Dry Eye = less than 15 mm of tears.. The smaller the number, the more severe the dry eye. A positive number change from Baseline indicates improvement. The eye with the lower value at baseline is used for each subject.
Time Frame	Baseline, Day 30

Outcome Measure Data

Analysis Population Description

Intent-to-Treat: All randomized patients

Arm/Group Title	Refresh Optive® Gel Drops	REFRESH LIQUIGEL®
Arm/Group Description	Refresh Optive® Gel Drops; 1-2 drops in each eye as needed at least 2 times daily for 30 days.	REFRESH LIQUIGEL®; 1-2 drops in each eye as needed at least 2 times daily for 30 days.
Measure Participants	94	94
Baseline	9.98 (7.178)	11.32 (8.496)
Change from Baseline at Day 30 (N=88, 86)	0.89 (5.601)	0.69 (6.479)

Adverse Events

Time Frame	Adverse events were recorded from Screening through Day 30.
Adverse Event Reporting Description	The Safety Population included all patients who received at least 1 dose of the study treatment. The Safety Population was used to assess adverse events and serious adverse events.
Arm/Group Title	Refresh Optive® Gel Drops		REFRESH LIQUIGEL®
Arm/Group Description	Refresh Optive® Gel Drops; 1-2 drops in each eye as needed at least 2 times daily for 30 days.		REFRESH LIQUIGEL®; 1-2 drops in each eye as needed at least 2 times daily for 30 days.
All Cause Mortality
	Refresh Optive® Gel Drops		REFRESH LIQUIGEL®
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Refresh Optive® Gel Drops		REFRESH LIQUIGEL®
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/94 (0%)		1/94 (1.1%)
Eye disorders
Hyphaema	0/94 (0%)		1/94 (1.1%)
Other (Not Including Serious) Adverse Events
	Refresh Optive® Gel Drops		REFRESH LIQUIGEL®
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/94 (7.4%)		5/94 (5.3%)
Eye disorders
Vision blurred	7/94 (7.4%)		5/94 (5.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

A disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 90 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.